Type 2 Diabetes Treatment Intensification 2

Question 1

Change in Blood Glucose as a Primary Marker

Answer 1

Not a suitable measurement as a surrogate outcome
- Can not be use as the only marker of success

Question 2

FDA Guidance for Evaluating Drugs used to treat Type 2 Diabetes

Answer 2

Have to prove that the therapy is no worse at increasing risks of adverse effects (myocardial infarction)

Question 3

Approvable
- Superiority
- No need for postmarketing study

Answer 3

Falls to the left of hazard ratio (less than 1)

Does not cross over Non Inferiority Boundaries:
- HR 1.3
- HR 1.8

Question 4

Approvable
- Non-Inferiority
- No need for postmarketing study

Answer 4

Crosses hazard ratio (equal or greater than 1)

Does not cross over Non Inferiority Boundaries:
- HR 1.3
- HR 1.8

Question 5

Approvable
- Non-Inferiority
- Need for postmarketing study

Answer 5

Crosses hazard ratio (equal or greater than 1)

Crosses Non Inferiority Boundary
- HR 1.3

Does not cross Non Inferiority Boundary
- HR 1.8

Question 6

Not Approvable
- Inferior

Answer 6

Does not cross hazard ratio (Greater than 1)

Crosses Non Inferiority Boundary
- HR 1.3
- HR 1.8

Question 7

Not Approvable
- Underpowered

Answer 7

Crosses hazard ratio (equal or greater than 1)

Crosses Non Inferiority Boundary
- HR 1.3
- HR 1.8

Question 8

Common CVOT Features

Answer 8

Inclusion Criteria identifies people at high risk of CV Outcomes
- CV Risk Factors
- Prior CV Events

Placebo Controlled Trial

Patient on Glucose Lowering Therapy according to guidelines

Primary Outcome: Major Adverse CV Events

Non-Inferiority Design

Question 9

Primary Outcomes of CVOT

Answer 9

Major Adverse Cardiovascular Events
- Nonfatal Myocardial Infarction
- Nonfatal Stroke
- Cardiovascular Related Death
- Hospitalization for Unstable Angina
- Hospitalization for Heart Failure

Question 10

Issues with CVOT

Answer 10

• Evidence is Hard to apply and generalize
• Unknown effects on microvascular
• Relative benefits of antihyperglycemic agents is unknown (Except: Glimepiride and Linagliptin)
• CV safety was not a major concern

Question 11

Slide 18

Question 12

What medication causes increased risk of amputation?

Answer 12

Canagliflozin

Question 13

DPP4i
- Safety Signal

Answer 13

Pancreatitis

Question 14

GLP1ra
- Safety Signal

Answer 14

Retinopathy
Gastroparesis
Suicide Risk

Question 15

SGLT2i
- Safety Signal

Answer 15

Genitourinary Infection
Diabetic Ketoacidosis
Fracture

Question 16

Thiazolidinediones
- Safety Signal

Answer 16

Heart Failure
Macular Edema
Distal Fractures (Women)

Question 17

Sulfonyulureas
- Safety Signal

Answer 17

Increased risk of Cardiovascular Events
- Do not use Glyburide
- If you have to use Gliclazide

Question 18

Diabetes Canada Guidelines
- Patient not reaching targets on noninsulin existing antihyperglycemic agent

Answer 18

Add a basal insulin regimen
- Decreased risk of hypoglycemia
- Decreased risk of weight gain

Basal is better than:
- Pre-mixed
- Bolus regimen

Question 19

Diabetes Canada Guidelines
- Patient is on basal insulin regimen and main priority is lowering risk of hypoglycemia. Which insulin should be used?

Answer 19

a) Glargine U-100/U-300, Detemir, Degludec > NPH
- Reduces risk of nocturnal and symptomatic hypoglycemia

b) Degludec or Glargine U-300 > Glargine U-100
- Reduces overall and nocturnal hypoglycemia
- Reduces risk of severe hypoglycemia in patients at high CV risk

Question 20

Diabetes Canada Guidelines
- Patient is on insulin and still not meeting targets

Answer 20

Adjust dose OR Add an additional antihyperglycemic agent
- DPP4i
- GLP1ra
- SGLT2i

These choices avoid weight gain and reduce risk of hypoglycemia

Question 21

Diabetes Canada Guidelines
- When adding a bolus insulin to additional antihyperglycemic agents

Answer 21

Rapid Acting (Aspart, Glulisine, Lispro) > Short Acting (Regular)
- Better glycemic control

Question 22

Diabetes Canada Guidelines
- How should insulin be initiated

Answer 22

Bolus is initiated using a stepwise approach
- Start with 1 injection at meals with additional mealtime injections if necessary
–> To achieve A1c reduction while lowering the risk of hypoglycemia

Better than initiating patient at bolus injection at every meal